α-Galactosylceramide-pulsed Human Dendritic Cells Can Ameliorate Post-Infarct Cardiac Remodeling and Failure in Mice — ASN Events
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α-Galactosylceramide-pulsed Human Dendritic Cells Can Ameliorate Post-Infarct Cardiac Remodeling and Failure in Mice (#139)

Akimichi Saito 1 , Naoki Ishimori 1 , Mikito Nishikawa 1 , Yoshihiro Masaki 1 , Shintaro Kinugawa 1 , Hiroyuki Tsutsui 1
  1. Hokkaido University Graduate School of Medicine, Sapporo, HOKKAIDO, Japan

Background:  Inflammatory mediators play a crucial role in the development of heart failure (HF). The activation of invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes, by α-galactosylceramide (α-GalCer) has been shown to attenuate post-infarct left ventricular (LV) remodeling and failure in mice. However, it activates iNKT cells temporarily and induces their anergy after repeated administration. In contrast, α-GalCer-pulsed human dendritic cells (α-GalCer/DC) can activate iNKT cells without inducing anergy even after repeated administration and have been investigated in the treatment of lung cancer. We aimed to investigate whether α-GalCer/DC could similarly ameliorate post-infarct LV remodeling and failure.

Methods and Results:  To obtain α-GalCer/DC, peripheral blood mononuclear cells were separated from 4 healthy male human volunteers (32±1.5 years) by apheresis, cultured with GM-CSF (800 U/mL) and IL-2 (100 U/mL) for 6 days, and pulsed with α-GalCer (100 ng/mL). Myocardial infarction (MI) was created in male C57BL/6J mice by ligation of the left coronary artery. The mice were divided into 2 groups according to the administration of either 3.0×106 α-GalCer/DC (n=32) or PBS (n=38) 1 and 4 days after the creation of MI, and followed during 28 days. Survival rate during 28 days after MI was significantly higher in α-GalCer/DC compared to PBS mice (63% vs. 37%, P<0.05). Echocardiography revealed that LV end-diastolic diameter was significantly reduced (5.1±0.1 vs. 5.8±0.2 mm, P<0.05) and LV fractional shortening was significantly elevated (15.1±0.6 vs. 9.8±0.6 %, P<0.05) in α-GalCer/DC group, accompanied by the significant decrease in LV end-diastolic pressure (9.7±1.2 vs. 13.5±1.8 mmHg, P<0.05) and heart weight/body weight (5.9±0.2 vs. 6.8±0.3 mg/g, P<0.05).

Conclusions:  α-GalCer/DC exerted a protective role against post-infarct LV remodeling and failure. It might be a novel therapeutic strategy against HF, which could be applicable to the patient.